Adiposity-Mortality Relationships in Type 2 Diabetes, Coronary Heart Disease, and Cancer Subgroups in the UK Biobank, and Their Modification by Smoking

Diabetes Care. 2018 Sep;41(9):1878-1886. doi: 10.2337/dc17-2508. Epub 2018 Jul 3.


Objective: The obesity paradox in which overweight/obesity is associated with mortality benefits is believed to be explained by confounding and reverse causality rather than by a genuine clinical benefit of excess body weight. We aimed to gain deeper insights into the paradox through analyzing mortality relationships with several adiposity measures; assessing subgroups with type 2 diabetes, with coronary heart disease (CHD), with cancer, and by smoking status; and adjusting for several confounders.

Research design and methods: We studied the general UK Biobank population (N = 502,631) along with three subgroups of people with type 2 diabetes (n = 23,842), CHD (n = 24,268), and cancer (n = 45,790) at baseline. A range of adiposity exposures were considered, including BMI (continuous and categorical), waist circumference, body fat percentage, and waist-to-hip ratio, and the outcome was all-cause mortality. We used Cox regression models adjusted for age, smoking status, deprivation index, education, and disease history.

Results: For BMI, the obesity paradox was observed among people with type 2 diabetes (adjusted hazard ratio for obese vs. normal BMI 0.78 [95% CI 0.65, 0.95]) but not among those with CHD (1.00 [0.86, 1.17]). The obesity paradox was pronounced in current smokers, absent in never smokers, and more pronounced in men than in women. For other adiposity measures, there was less evidence for an obesity paradox, yet smoking status consistently modified the adiposity-mortality relationship.

Conclusions: The obesity paradox was observed in people with type 2 diabetes and is heavily modified by smoking status. The results of subgroup analyses and statistical adjustments are consistent with reverse causality and confounding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / physiology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biological Specimen Banks / statistics & numerical data*
  • Body Mass Index*
  • Coronary Disease / complications
  • Coronary Disease / mortality*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / mortality*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / complications
  • Neoplasms / epidemiology
  • Neoplasms / mortality*
  • Obesity / complications
  • Obesity / epidemiology
  • Obesity / mortality
  • Overweight / complications
  • Overweight / epidemiology
  • Overweight / mortality
  • Risk Factors
  • Smoking / epidemiology
  • Smoking / mortality*
  • United Kingdom / epidemiology
  • Waist Circumference
  • Waist-Hip Ratio